In this study, EP was performed on the stomachs of healthy rats to evaluate the effect of EP on digestive function, serum marker level, and gastric structure over 28 days. The safety and efficacy of EP for both physiology and histopathology have been confirmed in a rat model. The digestive function and serum markers changed temporarily in the acute term but soon returned to normal within 28 days. The gastric wall remained intact without bleeding or perforation after EP.

The stomach is a vital organ for digestion and secretion. Gastric emptying, small intestinal transit, and gastric secretion are evaluation indices of digestive function [14, 15]. After EP, no significant change was observed for gastric emptying or secretion. The small intestine transit decreased immediately at 4 h post-EP, whereas it recovered to normal at 1d later. This study confirmed that EP has limited impact on digestive functions in a rat model; thus, EP is safe for digestive function when used as an ablation method.

Serum markers were observed to be dynamic in the rat model. Post-EP, inflammation factors may be regulated by multiple factors. By and large, anti-inflammatory factors tended to be reduced in the acute phase and recover later, while proinflammatory factors show the opposite effect. Angiogenesis is an important component of gastric erosion and ulcer healing. Prostaglandins, iNOS, and ghrelin are important for gastric mucosal protection and play a role in angiogenesis [16]. Prostaglandin can protect the gastric mucosa by inhibiting acid secretion, promoting mucus generation, and increasing mucosal blood flow [17]. The prostaglandin level in the treatment group tended to rise and reached a peak at 14 days post-EP. In addition, the concentration of serum NO, which can improve microcirculation and reconstruction of mucosa, reached a peak at day 3, then returned to normal on day 14, which is consistent with the histopathology of mucosal regeneration. Ghrelin increased from day 7 to day 14 post-EP, during which the mucosa regenerated rapidly.

The thermal-basis ablation technique could generate coagulation necrosis instantly after application as well as a peripheral transition zone around the ablation region due to the temperature gradient [18]. All these changes can be determined by gross observation. However, a non-thermal ablated lesion was caused without evident coagulation necrosis on gross inspection [19, 20]. The cell viability, gross pathology, and histopathology show dynamic change post-EP, which varies in different tissues [21]. In general, the tissue damage process caused by EP ends within 24 h, then the repair procedure begins on days 3 to 7 post-EP and is completed within 28 days.

Ensuring the integrity of the gastric wall is important for evaluating the safety of EP. Phillips et al. studied the influence of IRE on the small intestine structure of rats and demonstrated that the small intestine can be ablated completely by IRE without obvious gastrointestinal side effects [22]. The epithelium starts repairing 3 days after surgery. In this study, EP was applied to the stomach, and the change in gastric structure within 24 h was evaluated. The demarcated lesions with congestion on both gastric mucosa and serosa were caused by EP, which may be related to the vascular lock-in effect of EP [6]. Histopathology showed immediate death of cells contacting the electrode after EP, and complete ablation of the mucous layer at 24 h. The 0 h and 4 h samples also revealed massive numbers of positive cells in the TUNEL assay, indicating that cell apoptosis started as early as 0 h and reached a peak at 24 h post-EP in the ablated area. The E-cadherin and β-catenin complex are vital for the tight junction between epithelial cells, which is crucial for the formation of the gastric mucosal barrier that protects the mucosa from gastric acid [23, 24]. This study revealed that the expression of E-cadherin and β-catenin decreased in mucosal epithelial cells immediately post-EP, suggesting a tight junction break and destruction of the mucosal barrier, which promotes corrosion and necrosis of the gastric mucosa.

There were several limitations to this study. First, normal gastric tissue differs from tumour tissue; hence, the efficacy of EP for tumour ablation has not been sufficiently elucidated. Second, since digestive function is closely related to nerve distribution, more research is needed in more treatment locations. Third, given the disparity between humans and rats, the practical treatment process cannot be fully evaluated in this study and requires further investigation in large animal models and/or humans.



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